【摘要】目的：研究常染色体显性遗传视网膜色素变性(autosomal dominant retinitis pigmentosa, ADRP)家系中视网膜色素变性1（retinitis pigmentosa1,RP1）基因的突变特征及其在RP发病机制中的作用。
方法：运用聚合酶链反应和直接测序方法，对6个ADRP家系的47例成员和50 例对照者进行了RP1基因全编码区和邻近剪切位点的内含子区域序列突变的筛选与检测。运用单因素分析、多因素Logistic回归分析研究RP1基因点突变在RP发病中的作用。
结果：ADRP家系成员和对照组RP1基因第4外显子上检测出2个变异位点。在1691和1725密码子存在杂合的两种类型的密码子(S1691P,SerPro, TCT→CCT; Q1725Q,GlnGln，CAA→CAG)。ADRP家系成员中Ser1691Pro及Gln1725Gln位点突变率显著高于正常对照组 (χ2=11.202，P<0.05 )。
结论：RP1基因Ser1691Pro及Gln1725Gln位点多态性可增高RP的危险性，具有潜在的致病性，考虑为ADRP家系的易感基因。
【关键词】 视网膜色素变性 RP1基因 点突变
Analysis of the mutations of retinitis pigmentosa 1 gene in autosomal dominant retinitis pigmentosa family
ChunXia Li, XunLun Sheng, WenJuan Zhuang
Foundation item: National Natural Science Foundation of China (No.30260113)
Department of Ophthalmology, the Affiliated Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; Department of Ophthalmology, the First Hospital of Qingdao Economic & Technical Development Zone, Qingdao 266555, Shandong Province, China
Abstract
AIM: To detect and analyze the mutations in retinitis pigmentosa 1 (RP1) gene of members in several families affected by autosomal dominant retinitis pigmentosa (ADRP).
METHODS: The entire coding regine and splice sites of the RP1 gene of 47 affected from 6 ADRP and 50 unrelated controls were screened and detected by using polymerase chain reaction and direct DNA sequencing. Cosegregation analysis and population frequency studies were performed on patients with identified mutations. The clinical features were determined by complete ophthalmologic examinations.
RESULTS: Two mutations were detected in exon 4 of RP1 gene with ADRP and normal controls. Two heterozygotic changes at 1691 and 1725 codons (S1691P, SerPro, TCT→CCT; Q1725Q, GlnGln, CAA→CAG). The twopoint mutation rate of ADRP was significantly higher than that of normal control group (χ2=11.202,P<0.05).
CONCLUSION: These mutations of Ser1691Pro and Gln1725Gln in the RP1 can increase the danger of potential pathogens, which are the single nucleotide polymorphism of the RP1 gene. We can consider the susceptibility gene of ADRP family.
KEYWORDS: retinitis pigmentosa; retinitis pigmentosa 1 gene; point mutation
0引言
视网膜色素变性(retinitis pigmentosa, RP)是视网膜感光细胞和色素上皮细胞变性导致夜盲和进行性视野缺损的一组最常见遗传性致盲眼底病。在世界范围内RP的发病率约为1/3 500～1/4 000[1],造成约150万人视力损害，至今无有效的防治手段。目前随着遗传连锁定位分析及基因突变检测技术的广泛应用,对RP分子发病机制的研究已有一定的突破。RP大多呈单基因遗传,在遗传和表型上均具有较大的异质性。RP 的遗传方式可分为常染色体显性遗传( autosomal dominant retinitis pigmentosa,ADRP) 、常染色体隐性遗传( autosomal recessive retinitis pigmentosa , ARRP) 、X 连锁( X linked retinitis pigmentosa,XLRP)、双基因型( twogenotype retinitis pigmentosa) 和线粒体相关RP, 另有40%～50%患者如果无家族史则被称为散发型[25]。迄今为止已鉴定出32个候选致病基因与RP有关。而ADRP的研究主要集中在视网膜色素变性1（RP1）基因,视紫红质基因（RHO基因）和视网膜变性慢反应蛋白基因（RDS基因）。据文献的报道, 美国ADRP中,RHO和RP1突变约占到24%～30%[6]。我们对6个ADRP家系47例成员，（其中RP患者20例）和50例无血缘关系的正常人作为对照，对RP1基因进行检测分析，观察其突变的频率、特征及其在RP发病机制中的作用。
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